title: High levels of synaptosomal Na(+)-Ca(2+) exchangers (NCX1, NCX2, NCX3) co-localized with amyloid-beta in human cerebral cortex affected by Alzheimer's disease.
abstract: Synaptosomal expression of NCX1, NCX2, and NCX3, the three variants of the Na(+)-Ca(2+) exchanger (NCX), was investigated in Alzheimer's disease parietal cortex. Flow cytometry and immunoblotting techniques were used to analyze synaptosomes prepared from cryopreserved brain of cognitively normal aged controls and late stage Alzheimer's disease patients. Major findings that emerged from this study are: (1) NCX1 was the most abundant NCX isoform in nerve terminals of cognitively normal patients; (2) NCX2 and NCX3 protein levels were modulated in parietal cortex of late stage Alzheimer's disease: NCX2 positive terminals were increased in the Alzheimer's disease cohort while counts of NCX3 positive terminals were reduced; (3) NCX1, NCX2 and NCX3 isoforms co-localized with amyloid-beta in synaptic terminals and all three variants are up-regulated in nerve terminals containing amyloid-beta. Taken together, these data indicate that NCX isoforms are selectively regulated in pathological terminals, suggesting different roles of each NCX isoform in Alzheimer's disease terminals.
authors.affiliation: UCLA School of Nursing, Los Angeles, CA 90095, USA. ssokolow@sonnet.ucla.edu
authors.forename: Sophie
authors.initials: S
authors.lastname: Sokolow
authors.forename: Sanh H
authors.initials: SH
authors.lastname: Luu
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Headley
authors.forename: Alecia Y
authors.initials: AY
authors.lastname: Hanson
authors.forename: Taeree
authors.initials: T
authors.lastname: Kim
authors.forename: Carol A
authors.initials: CA
authors.lastname: Miller
authors.forename: Harry V
authors.initials: HV
authors.lastname: Vinters
authors.forename: Karen H
authors.initials: KH
authors.lastname: Gylys
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000032:analysis*; D002540:Cerebral Cortex / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D018613:Microscopy, Confocal; D020033:Protein Isoforms / Q000032:analysis; D019831:Sodium-Calcium Exchanger / Q000032:analysis* / Q000378:metabolism; D050825:Synaptosomal-Associated Protein 25 / Q000032:analysis; D013574:Synaptosomes / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D020033:Protein Isoforms; C101832:SLC38A3 protein, human; D019831:Sodium-Calcium Exchanger; D050825:Synaptosomal-Associated Protein 25; C110374:sodium-calcium exchanger 1